The extracellular matrix (ECM) is made up of fibronectin, laminin, collagen and elastic fibers, as well as numerous glycosaminoglycans and protoglycans. These ECM components are organized into a network of rope-like structures which underlie many tissues, such as, blood vessels, skin, tendons, ligaments, and lungs. Of these ECM components, elastin is unique in that it can be stretched to over 150 percent of its original length and rapidly returns to its original size and shape. This property provides tissues in which elastin is incorporated with the ability to resume their original form after stretching. Therefore, elastin and elastin fibers allow these tissues to maintain the resiliency, stretchability and shape of these tissues.
Elastic fiber formation (elastogenesis) is a complex process involving intracellular and extracellular events. Cells such as fibroblasts, endothelial cells, chondroblasts or vascular smooth muscle cells, first synthesize and secrete glycoproteins that form a microfibrillilar scaffold into the extracellular space. Tropoelastin, the soluble precursor peptide of elastin, is synthesized in these cells by ribosomes in the rough endoplasmatic reticulum and transported through the Golgi apparatus and secretory vesicles that deposit tropoelastin in the extracellular space. Once outside the cell, tropoelastin is assembled into long chains and covalently cross-linked by lysyl oxidase. During crosslinking, unique composite amino acids, desmosine and isodesmosine, which join the tropoelastin chains, are formed and insoluble elastin is created.
Elastin fibers are composed of two major components: an amorphous, elastin core which makes up the bulk (>90%) of the fiber; and the 10-12 nm microfibrilary component surrounding the elastin core made up of glycoproteins, such as, for example, fibrillins, fibulins and microfibril-associated glycoproteins (MAGPs). Elastin may also be interwoven with non-elastic collagen fibers to limit stretching and prevent tearing of certain tissues. Mature (insoluble) elastin is metabolically inert and remains the most durable element of extracellular matrix. In undisturbed tissues, mature elastin may last for the lifetime of the tissue.
Deposition of elastin in the ECM appears to be controlled on both the transcriptional level (tropoelastin mRNA message expression) and post-transcriptional level (tropoelastin message stability). Other post-transcriptional events which control secretion of tropoelastin monomers, extracellular assembly of tropoelastin, and regulation of cross-linking of tropoelastin may also control elastin deposition.
Human skin is made up of two layers: a superficial layer, the epidermis, consisting of epithelial tissue and a deeper layer, the dermis, primarily composed of connective tissue. Together these layers form skin of thickness from less than about 0.5 mm up to 3 mm or even 4 mm. The dermis is essentially ECM of the skin and mechanically supports the cells and blood vessels of the epidermis and modulates the hydration of the skin.
Primary elastinopathies have been directly linked to alterations in the elastin gene including supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS), Cutis Laxa, and a number of secondary elastinopathies which are caused by functional imbalance of other structural and auxiliary factors regulating elastic fiber deposition which has also been described including, for example, Marfan disease, GM-1-gangliosidosis, Morquio B, Hurler disease, Costello syndrome, Ehlers Danlos syndrome, and pseudoxanthoma elasticum (PXE). In the skin, a lack of elastin or genetic abnormalities affecting elastic fiber deposition lead to premature aging, most noticeably characterized by wrinkling and folding of the skin in children (pre-teenage) suffering from, for example, Costello Syndrome, Cutis Laxa and Pseudoxanthoma Elasticum. However, these conditions only affect elastic fibers in skin. Therefore, there is a high probability that development of wrinkles due to aging is caused by damage to or loss of elastic fibers in skin. Unfortunately, dermal fibroblasts lose their ability to make elastin by the end of puberty, and adult dermal fibroblasts cannot repair or replace damaged elastic fibers in skin leading to the irreversible formation of wrinkles.